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Objective This proof-of-principle-study evaluated the extent to which spontaneous activity (SA) of the muscle can be detected via non-invasive magnetomyography (MMG) with optically pumped magnetometers (OPM). Methods Five patients, who together exhibited all forms of SA (fibrillations, positive sharp waves, fasciculations, myotonic discharges, complex-repetitive discharges) with conventional needle electromyography (EMG), were studied by OPM-MMG and simultaneous surface EMG (sEMG) while at rest, during light muscle activation, and when a muscle stretch reflex was elicited. Three healthy subjects were measured as controls. SA was considered apparent in the OPM-MMG if a signal could be visually detected that corresponded in shape and frequency to the SA in the respective needle EMG. Results SA in the context of fasciculations could be detected in 2 of 5 patients by simultaneous OPM-MMG/sEMG. Other forms of SA could not be detected at rest, during light muscle activation, or after provocation of a muscle stretch reflex. Conclusions This proof-of-principle study shows that fasciculations could be detected non-invasively via a new method (OPM). Significance We show that other forms of SA are not detectable with current OPM and propose necessary technical solutions to overcome this circumstance. Our results motivate to pursue OPM-MMG as a new clinical neurophysiological diagnostic.

Objective The aim was to find a sensitive method to highlight the remodeling of the brain’s bioelectric activity in post-stroke repair. Methods Fifteen mild upper limb paretic stroke patients and age-matched healthy controls were included. Repeated trials of finger tapping around the 10th and 100th days after stroke onset were recorded with a 128-channel EEG. Power spectra and Inter Trial Coherence (ITC) calculations were synchronized to tappings. ITC was correlated with motor performance. Results ITC, in low frequency bands, designates the motor related bioelectric activity in channel space in both healthy subjects and patients. Ten days after stroke onset, delta-theta ITC was severely reduced compared to baseline, while three months later ITC reorganized partially over the ipsilesional central-parietal areas reflecting the improvement of motor networks. Decreased ITC in the central-parietal area remained significant compared to controls. Delta band ITC over the dorsolateral-prefrontal cortex correlates with the performance on Nine Hole Peg Test. At post-recovery, non-paretic hand tappings show significantly decreased delta-theta ITC over the supplementary motor area, which reflects network remodeling. Conclusions Inter Trial Coherence is a useful measure of brain reorganization during stroke recovery. Significance Delta- theta ITC is a sensitive indicator of impaired motor execution.

Objective A large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. Methods A total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. Results Patients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). Conclusions The HFO amplitude in ALS is increased, but does not predict survival. Significance The enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

Objectives Amyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. Methods In two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. Results Compared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P Conclusion The current study revealed that spinal inhibitory circuits are impaired in ALS. Significance These findings may provide insight for proposing new therapeutic approaches and following disease progression in humans.

Objective To explore the diagnostic accuracy of the split-hand index (SHI) for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) using sonographic assessment of muscle thickness. Methods We performed a prospective sonographic assessment of hand muscle thickness in 59 controls, 87 patients with ALS, and 33 patients with SMA. We determined the diagnostic accuracy of SHI for differentiating patients with ALS and SMA from controls. Results Patients with ALS and SMA had significantly lower muscle thickness and SHI values compared with controls. SHI showed excellent diagnostic accuracy for differentiating ALS from controls, and good diagnostic accuracy for differentiating SMA from controls. Conclusions SHI determined by sonographic measurement of hand muscle thickness seems to be a promising tool for the diagnosis of ALS and may be added easily when performing neuromuscular ultrasound. Significance SHI determined by sonographic measurement of hand muscle thickness can differentiate between healthy subjects and patients with ALS and SMA.

Introduction. Functional near-infrared spectroscopy (fNIRS) is a non-invasive method to measure changes in oxygenated- and deoxygenated-hemoglobin concentrations in response to neural activation during specific tasks and stimuli. In this study, we monitored the brain activity of the prefrontal cortex in subjects while driving to investigate the effects of speed on brain activity. Methods. Twenty healthy subjects with driving experience drove their own vehicles about 100 meters at any speed (5 trials) and at highest acceleration speed (5 trials) and were told to stop at the stop line. Sixteen channels of fNIRS recording were placed to overlie the prefrontal cortex of the subjects during driving. The distance between the stop line and the vehicle when the vehicle comes to a stop and oxygenated hemoglobin concentration was compared between driving at any speed and driving at the highest acceleration. Results. Variation in the distance between the stop line and the vehicle was significantly greater when driving at the highest acceleration compared to driving at any speed. Oxygenated hemoglobin concentration recorded in the prefrontal cortex was significantly greater while driving a car to a stop at the highest acceleration than at free speed. Conclusion. Our findings suggest that driving at highest acceleration speeds requires more attention resources than driving at any speed. We have shown that monitoring brain activity using fNIRS has advantages and usefulness of in real driving.

Introduction. Previous researches on peripheral filtering at the cochlear and brainstem levels toward auditory information by using BAEP measurement had been conducted. However, the results were still varied. This study was aimed to find out the effect of selective visual attention of watching movies towards the latency and amplitude of BAEP. Methods. This study involved 12 healthy subjects (9 males, 3 females) with right-ear dominance. The age of samples ranged from 21-52 years old, and the mean was 30.7 years. BAEP measurement was done in two conditions, eyes were closed and watching a silent action movie in 14 inches monitor with a view distance of 75 cm. Every subject was recorded two times for reproducibility using 4 Ag-Cl electrodes (Cz, Fz, A1, and A2) that were placed according to the International Electrode (10–20) Placement system. The stimulus was monoaural click-sound at the right ear with the intensity of 70 dB nHL, while noise-masking was given to the left ear. The measurements of latency and amplitude of wave I, wave V and interval peak latency of wave I-V were done. Results. This study showed that there were significant latency delay of wave I as much as. 0.068 ms or 3.81% (p = 0.006) and a decrease of amplitude as much as 0.043 µV or 26.34% (p = 0.001). But no significant different of latency and amplitude of wave V on two conditions - eyes closed and during watched movie (p > 0.05). The interval peak latency wave I-V of these two groups was not significantly different also with each value [4.022 ± 0.115 ms vs 3.989 ± 0.100 ms (p = 0.241)]. Conclusion. Selective visual attention by watching movies gave an inhibition effect toward the auditory pathway at the cochlear level, but no effect at the brainstem level.

Objective To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET). Methods Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects. Results In the LET, both the overall PKD patients and HypoPP patients had greater CMAP amplitude and area increments during exercise than healthy controls. At most 25% of PKD patients were identified from the normality with greater amplitude increment than the area. On the contrary, 50% of HypoPP patients were differentiated with greater area increment than the amplitude. More percentage of PRRT2− patients than PRRT2+ patients had abnormal average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum immediate amplitude decrement in the SET. Conclusions Distinct ET manifestations were found in PKD patients compared to normal controls and HypoPP patients. Significance Abnormal muscle membrane excitability might be involved in the mechanisms responsible for PKD.

Objective To compare comprehensive measures of scalp-recorded muscle activity in migraineurs and controls. Method We used whole-of-head high-density scalp electrical recordings, independent component analysis (ICA) and spectral slope of the derived components, to define muscle (electromyogram-containing) components. After projecting muscle components back to scalp, we quantified scalp spectral power in the frequency range, 52–98 Hz, reflecting muscle activation. We compared healthy subjects (n = 65) and migraineurs during a non-headache period (n = 26). We also examined effects due to migraine severity, gender, scalp-region and task (eyes-closed and eyes-open). We could not examine the effect of pre-ictal versus inter-ictal versus post-ictal as this information was not available in the pre-existing dataset. Results There was more power due to muscle activity (mean ± SEM) in migraineurs than controls (respectively, −13.61 ± 0.44 dB versus −14.73 ± 0.24 dB, p = 0.028). Linear regression showed no relationship between headache frequency and muscle activity in any combination of region and task. There was more power during eyes-open than eyes-closed (respectively, −13.42 ± 0.34 dB versus −14.92 ± 0.34 dB, p = 0.002). Conclusions There is an increase in cranial and upper cervical muscle activity in non-ictal migraineurs versus controls. This raises questions of the role of muscle in migraine, and the possible differentiation of non-ictal phases. Significance This provides preliminary evidence to date of possible cranial muscle involvement in migraine.

Objective To assess the impact of averaging multiple MUNIX trials on the follow-up of patients with amyotrophic lateral sclerosis (ALS). Methods We determined the percent relative change (%RC) of MUNIX, in healthy subjects and patients with ALS, by subtracting the MUNIX value in the second visit from the first. Both the mean of a set of three MUNIX (mean-MUNIX) and the first MUNIX sample (single-MUNIX) were evaluated. Then, we studied the sensitivity to detect relative changes over time and the statistical dispersion of the %RC from these two parameters. Results We found that the mean-MUNIX %RC has lower mean coefficient of variation than the single-MUNIX %RC in all muscles. The mean-MUNIX also resulted in more ALS patients with significant %RC, i.e., outside reference limits. Conclusion The mean-MUNIX resulted in less dispersed values of %RC in patients with ALS and thus, increased the precision of the technique. The mean-MUNIX resulted also in an increase in the sensitivity to track changes over time in these patients. Significance The mean-MUNIX should be considered in any ALS follow-up study as a more reliable approach and as a way of potentially reducing the sample size needed for the study.

Objective Healthy subjects can learn to use cognitive-emotional strategies to suppress their spinal nociception, quantified by the nociceptive flexor reflex (RIII reflex), when given visual RIII feedback. This likely reflects learned activation of descending pain inhibition. Here, we investigated if training success persists 4 and 8 months after the end of RIII feedback training, and if transfer (RIII suppression without feedback) is possible. Methods 18 and 8 subjects who had successfully completed feedback training were investigated 4 and 8 months later. Results At 4 months, RIII suppression during feedback and transfer was similar to that achieved at the final RIII feedback training session (to 50 ± 22%, 53 ± 21% and 52 ± 21% of baseline, all differences n.s.). At 8 months, RIII suppression was somewhat (not significantly) smaller in the feedback run (to 64 ± 17%) compared to the final training session (56 ± 19%). Feedback and transfer runs were similar (to 64 ± 17% vs. 68 ± 24%, n.s.). Concomitant reductions in pain intensity ratings were stable at 4 and 8 months. Conclusions RIII feedback training success was completely maintained after 4 months, and somewhat attenuated 8 months after training. Transfer was successful. Significance These results are an important pre-requisite for application of RIII feedback training in the context of clinical pain.

Introduction. Inhibition and facilitation of the muscle tone are important to improve the motor functions in stroke patients. Herein, we report the excitability of the anterior horn cells depressed after periodic thumb movements in our previous study. Periodic movements may be effective in inhibiting the muscle tone. However, the effect of the number of periodic movements on the excitability of the anterior horn cells with periodic movements is unclear. We investigated the excitability of the anterior horn cells with periodic movements after different number of movements. Methods. Twelve right-handed healthy subjects participated in this study. F-waves were recorded from the right abductor pollicis brevis with electrical stimulation to the right median nerve before, immediately after, and 2 and 4 min after a movement task. The movement task was periodic right thumb abductions at 2 Hz, and the number of movements was 10 or 20. For the statistical analysis, the Friedman’s test was used to compare the F/M amplitude ratio before, immediately after, and 2 and 4 min after the movement task. The lower rank test was compared using the Wilcoxon signed-rank test with Bonferroni correction. Significance was set below the 5% level. Results. The F/M amplitude ratio immediately after 10 periodic movements was lower than that before the task. However, the F/M amplitude ratio immediately after 20 periodic movements was the same as that before the task. Conclusion. The excitability of the anterior horn cells is inhibited after 10 periodic movements at 2 Hz.

A healthy subject will be examined with SFEMG in the frontalis muscle. First slight voluntary activation and then with electrical stimulation. Concentric needle electrodes will be used. Potential pairs of good and non-acceptable quality will be shown and comments will be made on pitfalls particularly in stimulation SFEMG. Remarks on criteria for signal acceptances will be made and a few examples of post-processing will be given.

Objective We found previously that use of a bimodal oddball design with synchronized pairs of audio-visual stimuli increased the sensitivity of the P300 wave to detect subclinical anxiety–depression in otherwise healthy subjects. Here, we wished to determine whether these P300 modulations would also be encountered when a clinical population comprised of patients with an adjustment disorder (AJD) was compared to healthy controls. Method Two groups, each comprised of twenty-five participants (AJD patients, and controls; N =50) had to detect deviant stimuli among frequent stimuli in an oddball task by clicking on a button. Separate blocks involving audio (A), visual (V) or bimodal congruent (AV) stimuli were used and compared. Results P300 amplitudes of the control group were higher than those displayed by AJD patients, but only in the bimodal AV oddball task, while unimodal (visual or auditory) oddball tasks did not reveal any significant differences. Conclusions The increased sensitivity of the bimodal P300 that we observed previously in subclinical anxiety–depression was also observed in AJD patients. Significance The impaired "bimodal congruence effect" in AJD suggests that these patients have altered integrative processes, which has potential implications for cognitive therapy.

Objective In this study we evaluated long-term effects of frontal beta EEG-neurofeedback training (E-NFT) on healthy subjects. We hypothesized that E-NFT can change frontal beta activity in the long-term and that changes in frontal beta EEG activity are accompanied by altered cognitive performance. Methods 25 healthy subjects were included and randomly assigned to active or sham E-NFT. On average the subjects underwent 15 E-NFT training sessions with a training duration of 45 min. Resting-state EEG was recorded prior to E-NFT training (t1) and in a 3-year follow-up (t3). Results Compared to sham E-NFT, which was used for the control group, real E-NFT increased beta activity in a predictable way. This increase was maintained over a period of three years post training. However, E-NFT did not result in significantly improved cognitive performance. Conclusion Based on our results, we conclude that EEG-NFT can selectively modify EEG beta activity both in short and long-term. Significance This is a sham controlled EEG neurofeedback study demonstrating long-term effects in resting state EEG.

Objective In patients with benign myoclonus epilepsy (ME), giant sensory-evoked potential (SEP) reflects the hyperexcitability of the sensory cortex. The aim of this study was to compare the effect of quadripulse transcranial magnetic stimulation (QPS) on the median nerve SEP between ME patients and healthy subjects. Methods Ten healthy volunteers and six ME patients with giant SEP participated in this study. QPSs at interpulse intervals (IPIs) of 5, 30, 50, 100, 500 and 1250 ms were applied over the left primary motor cortex (M1) for 30 min. The peak-to-peak amplitudes of N20 to P25 (N20–P25) and P25 to N33 (P25–N33) components were measured at the left somatosensory cortex. Results In healthy participants, the P25–N33 was bidirectionally modulated by QPS over M1, following the Bienenstock–Cooper–Munro (BCM) theory. The N20–P25 was not affected by any QPSs. In ME patients, the giant P25–N33 was potentiated after any QPSs. Furthermore, the N20–P25 was also potentiated after QPS at IPIs of 5, 30, 50 100 or 500 ms. Conclusions In ME patients, the cascade for long-term depression-like effects may be impaired. Significance The giant SEP was furthermore enhanced by QPS.

Objective To investigate hemodynamic trans-phasic fluctuations in Valsalva maneuver (VM) and relate them to adrenergic baroreflex sensitivity (BRSa) indices. Methods In a healthy population ( n =107) with a young age predominance (32±15years) systolic blood pressure (SBP) and BRSa indices in VM were studied. Results Augmented and Suppressed Autonomic Responses (AAR, 28%; SAR, 15%, respectively), in addition to Balanced Autonomic Response (BAR, 40%), were found. There was a predominance for an unbalanced SBP response (67% in AAR, 69% in SAR, vs. 53% in BAR) in subjects ages 20–29. Compared to BAR and AAR, SAR had insignificant female predominance (51% and 47% vs. 75% respectively, p >0.05). AAR had the highest alternative BRSa (BRSa 1 ) compared to SAR and BAR (26.73±17.97mmHg/s vs. 8.64±5.33mmHg/s and 15.68±10.40mmHg/s respectively, p Conclusions Qualitative evaluation revealed three distinct patterns in response to VM. Late phase II was found to be a key factor in VM patterns and as such, argues to include late phase II parameters such as hemodynamic and time indices in BRSa evaluation. Significance These findings may be of use in future evaluations when identifying mild autonomic dysfunction and/or distinguishing typical and atypical SBP patterns in a healthy population.

Objective To define and compare the input–output properties of 500 Hz and 100 Hz bone-conducted (BC) transmastoid stimulation when evoking cVEMPs and oVEMPs. The findings for 500 Hz were compared with those previously reported for air-conducted (AC) 500 Hz stimulation. Methods Twelve healthy subjects (18–57 years old) participated in this study, with simultaneous recordings of cVEMPs and oVEMPs bilaterally. Initial intensities of 138 dB (FL) were used and then reduced in 3 or 6 dB increments to 105 dB. Results For BC 500 Hz, like AC 500 Hz, the relationship between the stimulus and reflex output fitted a power law for most peaks, but not the initial peak of the oVEMP. Some of the subjects did not have early crossed oVEMP responses for BC 500 Hz but all did for 100 Hz. For BC 100 Hz, while the initial waveforms were similar, many of the peaks showed a tendency to saturate at the higher intensities. For both BC 500 Hz and 100 Hz, the initial (contralateral) oVEMP peaks had a higher threshold than for the (ipsilateral) cVEMP responses although this difference was more marked for 500 Hz. Conclusions BC 500 Hz shows similar properties to AC 500 Hz, consistent with an overlapping spectrum of afferents being excited by both, with bilateral effects for the BC stimulus. BC 100 Hz evokes more non-vestibular peaks, presumably from muscle afferents, for the SCM recordings but is a more reliable method of evoking the early crossed potentials of the oVEMP. Significance BC 500 Hz is a useful adjunct to the AC 500 Hz stimulus and has similar properties. The BC 100 Hz stimulus may be a more reliable method of evoking the early crossed oVEMP responses.

Objective To test the intra-individual reliability in response to anodal transcranial direct current stimulation (AtDCS). Methods 45 healthy subjects received AtDCS (1 mA, 13 min) in two separate sessions, 6–12 months apart. Motor evoked potentials were collected at baseline and then at 5-min intervals after AtDCS for 1 h. Short intracortical inhibition (SICI) was assessed at minutes 6 and 46 after AtDCS. Results AtDCS increased cortical excitability over minutes 0–30 post-stimulation in both sessions, with fair intra-individual reliability. 60% and 64% of subjects responded with the expected increase in cortical excitability in each session, respectively. 69% of the subjects maintained their response pattern between sessions during this timeframe. However, there were no significant effects on cortical excitability over the full hour post AtDCS in either session. SICI showed fair intra-individual reliability 6 min after AtDCS. Conclusion A change in cortical excitability in the first half-hour post-AtDCS may be a good predictor of the response in a subsequent session. Furthermore, minute 15 post-stimulation showed the maximum increase in cortical excitability in both sessions. Significance We show for the first time that intra-individual variability is lower than inter-individual variability, and with fair intra-individual inter-sessional reliability for 30 min after AtDCS-subjects are likely to maintain their response patterns to tDCS between sessions, with implications for experimental and therapeutic applications of tDCS.

Background Recently developed threshold tracking TMS (TT-TMS) paired pulse techniques have been shown to be of benefit in clinical diagnostic practice. Reduced Short Interval Cortical Inhibition (SICI) with increasing age has been shown in several studies using conventional paired-pulse TMS techniques. However, TT-TMS SICI parameters did not correlate to age in healthy subjects in a previous study (Shibuya et al., 2016). We aimed in this study to present the preliminary results of our normal material on TT-SICI and the relationship between SICI measurements and age. Material and methods Thirty-three healthy subjects (mean age: 51.06 ± 2.48, range: 23–77) were included. Paired-pulse TT-TMS was undertaken using a 90 mm figure-of-eight coil applied to the motor cortex, with currents generated by BiStim system controlled by Qtrac software. The motor evoked potential (MEP) response was recorded over the first dorsal interosseus (FDI). MEP amplitude was set to a target value of 0.2 mV, and the changes in the intensity of the test stimulus required to generate this target MEP were measured. The relationship between age and SICI measurements were analyzed using regression analysis. Results Resting motor threshold (RMT) (MSO, %) (mean: 54.43 ± 2.41) and SICI (%) at 1 ms (12.01 ± 1.86), 2.5 ms (11.02 ± 1.65), 3 ms (8.20 ± 1.69) and 1–7 ms (5.93 ± 1.12) on TT-TMS were analysed. RMT increased with increasing age (r = 0.45, p = 0.08), while age had an inverse relationship with SICI on 1 ms (r = −0.49, p = 0.003), 2.5 ms (r = −0.45, p = 0.008), 3 ms (r = −0.41, p = 0.019) and 1–7 ms (r = −0.41, p = 0.017). Conclusions SICI parameters closely relate to age for TT-TMS similar to previously reported conventional. Further studies are required with large groups of healthy subjects.

Objective To investigate the effects of focal muscle fatigue induced by electromyostimulation (EMS) on Anticipatory Postural Adjustments (APAs) during arm flexions performed at maximal velocity. Methods Fifteen healthy subjects performed self-paced arm flexions at maximal velocity before and after the completion of fatiguing electromyostimulation programs involving the medial and anterior deltoids and aiming to degrade movement peak acceleration. APA timing and magnitude were measured using surface electromyography. Results Following muscle fatigue, despite a lower mechanical disturbance evidenced by significant decreased peak accelerations (−12%, p p >.11 for all analyses). Conclusion The fatigue signals evoked by externally-generated contractions seem to be gated by the Central Nervous System and result in postural strategy changes which aim to increase the postural safety margin. Significance EMS is widely used in rehabilitation and training programs for its neuromuscular function-related benefits. However and from a motor control viewpoint, the present results show that the use of EMS can lead to acute inaccuracies in predictive motor control. We propose that clinicians should investigate the chronic and global effects of EMS on motor control.

Objective Arousal stimuli evoke bursts of skin sympathetic nerve activity (SSNA). SSNA usually contains sudomotor and vasoconstrictor neural spikes. The aim of this study was to elucidate which components of event-related potentials (ERPs) are related to sudomotor and vasoconstrictor responses comprising arousal SSNA bursts. Methods We recorded SSNA from the tibial nerve by microneurography, with corresponding sympathetic skin response (SSR), sympathetic flow response (SFR), and ERPs in 10 healthy subjects. Electrical stimulation of the median nerve was used to induce arousal responses. ERPs were classified by the occurrence of SSR and SFR. Results SSNA bursts followed by SSR were associated with larger P300 than SSNA bursts followed by no SSR. For N140, no difference in the amplitude was found between SSNA bursts with and without SSR. SSNA bursts followed by SFR were associated with larger N140 than SSNA bursts followed by no SFR. However, there were no differences in the amplitude of P300 between SSNA bursts with and without SFR. Conclusions Sudomotor and skin vasoconstrictor responses to arousal stimuli were differently associated with distinct ERP components. Significance The possibility that sudomotor and skin vasoconstrictor activities comprising arousal SSNA reflect different stages of the cognitive process is suggested.

Objective The symptoms with optic ataxia suggest that simple and visually guided hand movements are controlled by 2 different neural substrates. To assess the differential frequency-coded posterior parietal cortex (PPC) role in planning visuo-motor goal-directed tasks, we studied the action specificity of event-related desynchronization (ERD) in this area. Methods We investigated cortical activity by electroencephalography, while 16 healthy subjects performed self-paced reaching or wrist extension (control) movements. Time–frequency representations were calculated for each movement during the preparatory period. Results ERD dynamics in upper alpha-band indicated that preparing a goal-directed action activates contralateral PPC to the moving hand around 1.2 s before starting the movement, while this activation is later (around 0.7 s) in preparing a not-goal-directed action. The posterior dominant rhythm had peak frequency of lower alpha-band at bilateral parietal. Conclusions Posterior parietal cortex encodes goal-directed movement preparation through upper alpha-band activity, whereas general attention is processed via lower alpha-band oscillations. Significance Preparing to reach an object engages posterior parietal cortex earlier than a not-goal directed movement.

Introduction Studies with transcranial direct current stimulation (tDCS) have shown that anodal tDCS of the cerebellar hemispheres leads to faster adaptation of arm reaching movements to visuomotor rotation and force field perturbations in healthy subjects ( Galea et al., 2011 , Herzfeld, 2014 ). Objectives The first aim of the present study was to replicate the findings mentioned above. The second aim was to investigate whether tDCS effects differ depending on the onset of stimulation, that is during or after an initial baseline phase. Patients and Methods A total of 120 healthy and right-handed subjects (60 females, aged 18–31 years, mean 23.2 ± 2.7) were tested. Subjects moved a cursor with a two-joined manipulandum to one of eight targets presented on a screen. There were three baseline blocks, one adaptation block and three washout blocks. 60 subjects performed a force field (FF) task, 60 subjects a visuomotor adaptation task (VM). During the adaptation block, a velocity-dependent clockwise perpendicular force (23 N ·m−1·s−1 was applied in FF and a 30° clockwise rotation in VM. Equal numbers of subjects received anodal, cathodal or sham stimulation over the right cerebellum beginning either in the third baseline or in the adaptation block. The maximum error (ME), final error (FE) and perpendicular velocity 55 ms after movement onset (PV) were assessed. Results During FF and VM adaptation subjects significantly improved regarding ME, FE and PV (p 0.05). The same was true for the washout blocks. Conclusion Our results show that prior possible clinical application, future experiments are needed to determine which cerebellar tDCS and task parameters lead to robust tDCS effects. Funded by ELAN and DFG TI 239/16-1.

Objective Patients with Parkinson’s disease often experience difficulties in adapting movements and learning alternative movements to compensate for symptoms. Since observation of movement has been demonstrated to lead to the formation of a lasting specific motor memory that resembled that elicited by physical training we hypothesize that mu-rhythm desynchronization in response to movement observation is impaired in Parkinson’s disease. Method In a pilot study with nine patients with Parkinson’s disease at a Hoehn and Yahr stage of I or II and eleven age-matched controls, we tested this hypothesis by comparing the event related desynchronization (ERD) patterns from the EEG recorded during the observation of hand action and baseline videos. Results Healthy subjects showed normal bilateral ERD of the mu-rhythm. In patients with Parkinson’s disease this distinct ERD pattern was lacking. Conclusion The results of this study suggest that event-related mu-rhythm desynchronization is impaired in Parkinson’s disease, even at early stages of the disease. Significance Studying event-related mu-rhythm desynchronization dysfunction in Parkinson’s disease patients may enhance our understanding of symptoms as impaired motor learning.

Objective Sleep spindles have been suggested as surrogates of thalamo-cortical activity. Internal frequency modulation within a spindle's time frame has been demonstrated in healthy subjects, showing that spindles tend to decelerate their frequency before termination. We investigated internal frequency modulation of slow and fast spindles according to Obstructive Sleep Apnea (OSA) severity and brain topography. Methods Seven non-OSA subjects and 21 patients with OSA contributed with 30min of Non-REM sleep stage 2, subjected to a Matching pursuit procedure with Gabor chirplet functions for automatic detection of sleep spindles and quantification of sleep spindle internal frequency modulation (chirp rate). Results Moderate OSA patients showed an inferior percentage of slow spindles with deceleration when compared to Mild and Non-OSA groups in frontal and parietal regions. In parietal regions, the percentage of slow spindles with deceleration was negatively correlated with global apnea-hypopnea index ( r s =−0.519, p =0.005). Discussion Loss of physiological sleep spindle deceleration may either represent a disruption of thalamo-cortical loops generating spindle oscillations or some compensatory mechanism, an interesting venue for future research in the context of cognitive dysfunction in OSA. Significance Quantification of internal frequency modulation (chirp rate) is proposed as a promising approach to advance description of sleep spindle dynamics in brain pathology.

Introduction In the past, the suppression of the pineal hormone melatonin by light has been investigated in several studies, frequently using small samples and only male subjects. Whereas the nocturnal melatonin production is thought to decrease with age, our knowledge about the extent of the light-induced melatonin suppression depending on sex and age is only limited. Our study addressed this issue in more details. Methods Subjects for this study were pre-screened for the onset of melatonin production in the evening hours. In total, 94 healthy subjects between 18 and 73 years were enrolled (42 men/52 women). All of them had a regular sleep-wake schedule and were morning or intermediate types according to the Ostberg-Horne-Ostberg morningness-eveningness questionnaire (scores: 41–73). They completed 4 evening laboratory sessions (19:00–23:00 h) predominantly in a weekly interval. The light protocol for each session consisted of a 2-h dim light ( Results After 2 h of dim-light condition all enrolled study participants showed an increase in melatonin production versus baseline of different magnitude. One hour of warm-white light at 500 lx (0.264 W/m2) caused very variable suppression of melatonin which did not exceed about 64% in both sexes. The average melatonin suppression over all subjects was 30.2% with sex related differences in the frequency of strong suppression, being higher in men. The inter-individual variability in melatonin suppression by warm-weight light was not related to the age of study participants. We also proved the impact of physical activity. Men with low physical activity showed relatively small plasma melatonin concentrations after 2 h dim-light condition, but a high sensitivity to the warm-white light applicated. Conclusions The obvious individual variability in the sensitivity of melatonin production for artificial light in the evening with possible sex but not clear and simple age related differences could be a critical factor in our understanding of light effects. Levels of physical activity in the leisure time could be a masking factor which should be adequately controlled in similar studies.

Introduction We describe a new nerve conduction study technique with reference values for the three branches of the supraclavicular nerve (SCN) in young healthy subjects and application of it in two patients. Methods The recording electrode was placed at the posterior border of the sternocleidomastoid muscle, 6–7 cm from the sternoclavicular joint. SCN branches were stimulated just below the clavicle, 2.5 cm, 7 cm and 10.5 cm lateral to the sternoclavicular joint. Results Twenty healthy volunteers (ten men and ten women), 19–38 years, mean 25.9 years (SD 6.3) and two case reports with SCN lesions. The mean conduction velocities of the SCN branches were 70–78 m/s (SD 8–10 m/s), and amplitudes 3–4 μ V (0.9–2.0 μ V). There were no differences between the sides or genders. Conclusion NCS of the three SCN branches was feasible in all subjects, providing reference values of this new technique. The method was useful in verifying SCN lesions in two patients.

Introduction High resolution ultrasonography (HRUS) of peripheral nerves is an emerging tool in investigating peripheral nerves, complementary to electrodiagnostic tests, and it is commonly performed using a linear array transducer with upper frequencies between 12 and 19 MHz. Since 2016 a very-high-resolution US (VHRUS) device is available for clinical use (Vevo-MD) that incorporates transducers with upper frequencies of 48 MHz (pixel resolution 50 μ m, depth 2.3 cm) and 70 MHz (pixel resolution 30 μ m, depth 1 cm). Our aim was to investigate the potential role of VHRUS in the assessment of the posterior tibial nerve (PTN) and sural nerve (SN) healthy echographic features being both commonly involved in peripheral neuropathies. Methods We studied these nerves (at the ankle) in 10 healthy subjects, comparing images obtained with VHRUS to those usually obtained with a 19 MHz HRUS. In particular, we compared 19 vs 48 MHz for PNT and 19 vs 70 MHz for SN. We measured nerves’ areas, perimeters and fascicular pattern obtained from the images acquired with both devices by using dedicated offline post-processing tools, and we compared the respective values. Results Our data show significant agreement in the measurements of area and perimeter obtained with both devices. However, using VHRUS we experienced a much higher degree of confidence in visualizing both nerves and their internal structure thanks to its superior spatial resolution. We also noticed that scanning depth was always sufficient for this diagnostic task. Conclusion VHRUS shows promising advantages compared with HRUS although further studies are needed to validate its use also in subjects with well-established peripheral neuropathies.

Introduction The paired-pulse transcranial magnetic stimulation (TMS) is an effective and non-invasive way to assess cortical excitability. The threshold tracking TMS (TT-TMS) was developed to overcome the variability in motor evocated potentials (MEP) amplitude caused by traditional TMS methods. Recently, TT-TMS has been widely used as a neurophysiological biomarker for upper motor neuron involvement. To date, the effect of age and gender has been assessed in healthy subjects while the influence of genetic backgrounds have not been well documented. However, previous study revealed that Chinese subjects tended to have significantly different TMS parameters compared with Caucasian subjects utilizing a constant TMS protocol. As such, we investigate effects of genetic backgrounds on cortical excitability by TT-TMS techniques. Methods Cortical excitability was evaluated on twenty-five Chinese healthy subjects (10 males, 15 females; mean age = 28.80 ± 8.16 years) and eighteen matched Caucasian healthy controls (10 males, 8 females; mean age = 32.67 ± 8.49 years) by recording from the dominant abductor pollicis brevis (APB) muscle. A paired-pulse protocol was used to measure the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). MEP and cortical silent period (CSP) duration were compared between two groups by single-pulse TMS. Results Compared with Caucasian people, Chinese subjects exhibited an increased RMT (Chinese 59.04 ± 8.89%; Caucasian 48.04 ± 10.47%[mean ± SE], p = 0.001). Although Chinese group had a trend of decreased cortical inhibition with a reduced average SICI (Chinese 9.03 ± 9.95%; Caucasian 12.23 ± 8.35%, p = 0.273) and increased ICF (Chinese 0.003 ± 6.68%; Caucasian −0.17 ± 5.95%, p = 0.933) the differences were not significant. In terms of single-pulse TMS, there were no significant differences between two groups in CSP duration(Chinese 173.46 ± 38.54 ms; Caucasian 184.76 ± 36.7 ms, p = 0.339) and MEP/CMAP ratio (Chinese 22.85 ± 14.03%; Caucasian 22.78 ± 15.00%, p = 0.99). Conclusion In this study, TT-TMS is proven to be a reliable method to assess cortical function in Chinese subjects. Of further relevance, these findings also provide evidence for interpreting the effects of genetic backgrounds on TMS variables in clinical practice.

Introduction Sensory and motor evoked potentials (SEP; MEP) can be used to measure quantitatively the extent of delayed signal conduction in multiple sclerosis (MS). They may be useful to monitor disease course and even serve as biomarkers in clinical trials (Hardmeier et al., 2017). Here we estimate the detectable differences in group means and in longitudinal group changes for different sample sizes accounting for physiological and rater-related variability. Methods 15 healthy subjects were evaluated twice within 30 days with median and tibial SEP and upper (UL) and lower limb (LL) MEP in three centers 1-3 according to a common standardized protocol in keeping with IFCN recommendations. Four neurophysiologists (FJ, MH, PA, PF) independently marked all curves blinded to their previous ratings using a web-based tool (EPMark; HB, MH, PF). N20, P40, shortest and mean cortico-muscular-latencies (CML) were analyzed; central (motor) conduction times were omitted due to lower test-retest-reliability. In addition, the sum of the z-transformed results from each test was divided by number of tests to yield a quantitative EP-score (qEPS). Mixed effect models using results of time-points 1 and 2 as combined outcomes were employed to calculate the standard error (SE) of a group mean of cross-sectional measurements or longitudinal changes. The respective SE formulas were used to calculate the difference d detectable with a power of 90% [d = (1.96 + 1.28) ∗ sqrt( SE 1 2 + SE 2 2 ) -2CoV] as a function of group size assuming a central reading center. Covariance between group means by common influence of raters on both groups was ignored for a more conservative estimate. Results For a sample size of n = 60, cross-sectional group mean difference (d1) is estimated to range from 0.6 to 2.1 ms (N20: 0.6, P40: 1.5; CML-UL [shortest/ mean]: 1.4/1.2; CML-LL: 1.7/2.1), and longitudinal mean group difference (d2) from 0.4 to 2.7 ms (N20: 0.4, P40: 1.0; CML-UL: 1.1/0.8; CML-LL: 1.6/2.7). For a sample size of n = 100, d1 ranged from 0.5 to 2.0 ms (N20: 0.5, P40: 1.2; CML-UL: 1.1/1.0; CML-LL: 1.4/2.0), and d2 from 0.4 to 2.6 ms (N20: 0.4, P40: 0.8; CML-UL: 0.9/0.7; CML-LL: 1.5/2.6). For qEPS [including shortest or mean CML], d1 was 0.5/0.4 ms for n = 60, and 0.4/0.3 ms for n = 100; d2 was 0.3/0.2 ms for n = 60 and 0.2/0.2 for n = 100. Conclusion Quantitative evaluation of combined SEP and MEP is possible in a multicenter setting with an independent reading center and allows reliable detection of significant differences in small groups of subjects. When evaluating an intervention, significant changes of EP results at an individual level help to identify responders, while significant changes at a group level may help to determine the biological effectiveness of an intervention. However, variability may be higher in patients and thus, consecutively, estimates of sample size. Supported by an unconditional research grant from Biogen Inc. MA, USA, which had no influence in planning the study or data analysis.

Introduction Sensory and motor evoked potentials (SEP; MEP) can be used to measure quantitatively the extent of delayed signal conduction in multiple sclerosis (MS). They may be useful to monitor disease course and even serve as biomarkers in clinical trials (Hardmeier et al., 2017). Here we evaluate physiological and rater-related variability to determine the minimal significant change between two measurements intra-individually. Methods 15 healthy subjects were evaluated twice within 30 days with median and tibial SEP and upper (UL) and lower limb (LL) MEP in three centers1–3 according to a common standardized protocol in keeping with IFCN recommendations. Four neurophysiologists (FJ, MH, PA, PF) independently marked all curves blinded to their previous ratings using a web-based tool (EPMark; HB, MH, PF). In SEP, N13, N20 and N22, P40, in MEP, cortico-muscular- (CML) and spinal-muscular-latencies were marked. N20, P40, shortest and mean CML, and central (motor) conduction times (CCT; CMCT) were analyzed. Mixed effect models were calculated using results of (a) 1st and 2nd rating of identical baseline curves (model 1), and (b) 1st baseline and follow-up rating (model 2) as combined outcomes. Based on model 2, confidence intervals (CI) were calculated for the difference of a repeated measurement of the same curve. Results Intra-class-correlation coefficient (ICC) for intra-and inter-rater reliability (model 1) was very high in median SEP (N20: 0.97; CCT: 0.85) and tibial SEP (P40: 0.95; CCT: 0.89). In MEP, ICC was higher when mean CML (UL: 0.94; LL: 0.90) or mean CMCT (UL: 0.88; LL: 0.91) was used instead of shortest CML (UL: 0.80; LL: 0.78) or shortest CMCT (UL: 0.65; LL: 0.81). As CCT and CMCT showed lower ICC, only CML, N20 and P40 were further analyzed. Total variance in model 2 ranged from 0.9 to 6.4 ms (N20: 0.9, P40: 6.4; CML-UL [shortest/mean]: 4.8/4.1; CML-LL: 5.8/3.7), mainly accounted for by inter-subject variability (64–79%); estimation of center effects was unreliable. 80%-CI ranged from 0.4 to 1.5 ms (N20: 0.4, P40: 1.3; CML-UL: 1.5/1.1; CML-LL: 1.1/0.9), 95%-CI from 0.7 to 3.0 ms (N20: 0.7, P40: 2.6; CML-UL: 3.0/2.2; CML-LL: 2.2/1.7). Conclusion Main SEP components (N20, P40) and MEP cortico-muscular latencies show higher reliability than central conduction times. Mean instead of shortest CML further improves reliability. Intra-subject differences in individual tracts exceeding 0.4 to 3.0 ms (depending on test and CI level) most likely reflect true underlying changes. These numbers may be used to define responders to remyelinating therapies in MS. However, these confidence intervals may be higher in patients and have to be validated in a larger sample. In group level analyses, variability is much less important as over- and underestimation counterbalance each other. Supported by an unconditional research grant from Biogen Inc. MA, USA , which had no influence in planning the study or data analysis.

Background Step initiation can vary according to attentional resources. Components of visuospatial attention (alerting, orienting, and executive control or conflict resolution) have shown to be able to modulate specifically anticipatory postural adjustments (APAs) and step execution phase, and can be assessed simultaneously within a single paradigm: the “Attention Network Test” (ANT). The present study aims to a better understanding of the interaction between visuospatial attention and step initiation in a healthy population through the observation of: (1) the modulation of step initiation while performing the ANT and (2) the potential modifications of cortical motor preparation. Material and methods Thirty-two healthy subjects performed an attentional task adapted from the ANT and combined with step initiation. Cortical activity during movement preparation (APA) and execution was assessed via high-resolution encephalography. Results Step initiation was particularly perturbed in conflict resolution condition. Conflict resolution also affected event-related spectral perturbations (ERSPs) in alpha and beta bands: movement-related desynchronization over the sensorimotor cortex occurred earlier and was longer and of higher amplitude after response to a target with incongruent flankers. Conclusions Tasks with attentional load such as conflict resolution lead to an alteration of step initiation and concomitant modifications of ERSPs during APAs. The ANT combined with step initiation could be therefore used to better understand pathologies such as Parkinson’s disease with gait akinesia.

Background There are technical limitations in the radial nerve studies in the upper arm using surface electrodes. One of the limitations is that stimulation at the axilla and Erb‘s point stimulates the entire brachial plexus along with the radial nerve. Material and methods Twenty-one healthy volunteers, 55 patients with compressive neuropathies of the radial nerve in the spiral groove and 22 patients with complete radial nerve injuries were studied. Control group (65 radial nerves) consisted of healthy subjects and patients with the undamaged side. Stimulation was carried out at: (1) the distal part of lateral brachium (distal point); (2) Erb’s point (proximal point); (3) the middle part of medial brachium – median and ulnar nerves (additional point). CMAP area recorded from the extensor digitorum was analyzed. Conduction block (CB) in percentage was calculated using the formula: ((distal CMAP + additional CMAP) − (proximal CMAP)) × 100/(distal CMAP + additional CMAP). Results In control group and patients with complete nerve injury CB was not registered (4.2 ± 9.8% and −1.7 ± 11.7% respectively), whereas in patients with compressive radial nerve neuropathy CB was 61.2 ± 11.2% (P Conclusion Median and ulnar nerves stimulation in the middle part of medial brachium is recommended as an additional brachium diagnostic point for radial nerve CB determination.

Background Compression over a peripheral nerve leads to several changes in structural and physiological properties of that nerve. Paranodal myelin abnormalities and impaired axonal transport are some pathological incidents defined after acute compression. Materials and methods In sixteen ALS patients and 16 controls, CMAP Scan curves were recorded from first dorsal interosseus (FDI) muscle by stimulating ulnar nerve at elbow before compression, compression in 5 consecutive CMAP scanning cycles, and after compression. Stimulus intensities needed to elicit 10% and 90% of CMAP and step number and step% were calculated for each scan. As a further comparison, areas under CMAP scan curves were examined using natural values, percentages, and differences between compression (comp) cycles. Results For both patients and controls, conventional CMAP scan parameters were not significantly different in consecutive cycles. During compression, a tendency of reduction in area under CMAP scan curve of ALS patients (164.8 mVms, 156.3 mVms, 146.5 mVms, 142.1 mVms, 142.7 mVms, 137 mVms, and 174.9 mVms for pre-comp, 1st comp, 2nd comp, 3rd comp, 4th comp, 5th comp, and post- comp cycles, respectively) and a tendency of increase in CMAP scan curve area of healthy subjects (283.3 mVms, 315.6 mVms, 298.5 mVms, 319.7 mVms, 336.1 mVms, 361.4 and 308.1 mVms for pre-comp, 1st comp, 2nd comp, 3rd comp, 4th comp,5th comp, and post- comp cycles, respectively) were observed. Conclusions Probably due to incidental changes in nerve excitability, ALS patients mostly reacted differently to nerve compression when compared with healthy subjects.